BREAST & PROSTATE CANCER Calcium and Vitamin D Recommendations for Patients

Undergoing Hormonal Therapies for Treatment February 25, 2016

Emily Rohan & Amber Smith

Survivor Rates Breast Cancer: The American Cancer Society's estimates in the United States for 2016 are 246,660 new cases of invasive breast cancer will be diagnosed in women

Stage 5-year Relative Survival Rate

0 100%

I 100%

II 93%

III 72%

IV 22%

Prostate Cancer: The American Cancer Society’s estimates for prostate cancer in the United States for 2016 are about 220,800 new cases of prostate cancer

Stage 5-year relative

survival rate

local nearly 100%

regional nearly 100%

distant 28%

Objectives 1.  Review osteoporosis and the mechanism of bone remodeling

2.  Explain current treatments for breast and prostate cancer and how these lead to decreased bone mineral density

3.  Discuss possibilities of Calcium and Vitamin D intake/supplementation for prevention and treatment of cancer induced bone loss using evidenced based research

a.  Consider the strengths and weaknesses of the current literature

4.  Provide Calcium and Vitamin D recommendations of doses for Breast and Prostate Cancer Survivors

5.  Identify future research needed on this topic

Purpose: Current Cancer Therapies & Osteoporosis Relationship

Breast Cancer Therapies:

Osteoporosis is a known concern in postmenopausal women

Especially a concern in postmenopausal BC survivors

BC treatments such as chemotherapy, SERMS (Selective Estrogen Receptor Modulators) and aromatase inhibitors (AI’s), increase bone resorption without also increasing bone formation --> bone loss and reduced BMD

Prostate Cancer Therapies:

Osteoporosis is also prevalent in older males, however not as common as women

Androgen Deprivation therapy is the primary treatment for localized/nonmetastatic PC

Decreased BMD/osteoporosis is a common side effect in men undergoing ADT due to the increase in hypogonadism

Bone Mineral Density (BMD)

•Definition: the amount of minerals (mostly calcium and phosphorus) contained in a certain volume of bone.

•BMD measurements are used to diagnose osteopenia/osteoporosis

http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=415875

Osteoporosis: Definition & Markers

-or clinical fragility fracture regardless of BMD -or incidentally found asymptomatic vertebral compression fracture

Golob AL, Laya MB. Osteoporosis: Screening, prevention, and management. Med Clin North Am. 2015;99(3):587-606. http://nof.org/articles/743

Normal Bone Remodeling

Lustberg MB, Reinbolt RE, Shapiro CL. Bone health in adult cancer survivorship. J Clin Oncol. 2012;30(30):3665-3674.

Calcium + Vitamin D intake

INCREASE in Ca absorption

Inhibits PTH secretion

Removes calcium from blood into bone

DECREASED Calcium + Vitamin D intake

DECREASED intestinal Ca absorption

Stimulates PTH secretion

Calcitriol to Calcitonin

Inhibits conversion to calcitonin

Removes calcium from bone into blood

Bone Remodeling with Cancer Treatment

Lustberg MB, Reinbolt RE, Shapiro CL. Bone health in adult cancer survivorship. J Clin Oncol. 2012;30(30):3665-3674.

Androgen Estrogen

Hormone Cancer Treatment

Osteoporosis Medications Target osteoclasts

Osteoclasts contribute to bone resorption = bone loss

Osteoporosis medications work to suppress osteoclasts = decrease bone resorption

Class of drugs commonly used = bisphosphonates

Osteoporosis Treatments Drug Category Drug Names Mechanism of Action Side effects Notes

Bisphosphonates Alendronate, Ibandronate, Risendronate, Zoledronic acid

Decreases bone resorption by reducing osteoclast activity

Esophageal irritation, osteonecrosis of the jaw (rare- long term tx), atypical femur fractures (rare-long term tx)

Should be taken on empty stomach

Parathyroid hormone antagonist

Calcitonin Decreases bone resorption by reducing osteoclast activity

Rhinitis (nasal mucosa irritation), increased malignancy risk

*Not a first line agent

Parathyroid Hormone

Teriparatide Increases bone formation Leg cramping, nausea, dizziness, increased osteosarcoma risk

Should be replaced by bisphosphates when stopped. Tx duration not to exceed 18-24 mos. Avoid in pts with increased risk of osteosarcoma

Estrogen Conjugated estrogens Suppress osteoclasts. Decreases overall bone resorption

DVT, PE, CVD (women > 10 yrs post menopause), Stroke, Invasive BC

*Not a first line agent

Estrogen Agonist/Antagonists (aka SERMS)

Raloxifene Suppress osteoclasts via acting as estrogen agonist

DVT, PE, hot flashes, leg cramping

For women with BC hx and who have osteoporosis

RANK Ligand Inhibitor

Denosumab Decreases bone resorption by reducing osteoclast activity

Hypocalcemia, increased risk of cellulitis, osteonecrosis of jaw, atypical femur fractures

No dosing restrictions according to renal fx

Medications contribute to loss of bone density

Golob AL, Laya MB. Osteoporosis: Screening, prevention, and management. Med Clin North Am. 2015;99(3):587-606.

Pathophysiology and Mechanism of Bone Loss

Pathophysiology of Breast Cancer Breast Cancer: uncontrolled growth of abnormal cells in the glands or ducts of the breast.

Breast cancer is characterized by 3 specific cell surface receptors:

1. ER = estrogen receptor (grows in response to estrogen) 2. PR = progesterone receptor (grows in response to progesterone) 3. HER2 = human epidermal growth factor receptor (characterized by HER2 + and HER2 -. HER2 + breast cancer is a type where cells make too much of a protein known as HER2/neu, while HER2 - breast cancer do not overexpress the HER2/neu protein. Treatment depends on: ●  Type of breast cancer ●  Tumor size ●  Stage of cancer ●  Whether or not the female has completed menopause ●  General health of the patient

Breast Cancer Hormonal Therapies Type Explanation

SERMS (Selective Estrogen Receptor Modulators) -  Inhibit the growth of breast cancer cells by competitive antagonism of the estrogen receptor (ER). SERMs are also known as anti-estrogens.

-  Utilized in ER + (estrogen receptor positive) breast cancers -  Utilized in pre and postmenopausal women -  Drug names: Tamoxifen, Raloxifene, Toremifene

AI’s (Aromatase Inhibitors) -  AI’s suppress plasma estrogen levels by inhibiting/inactivating aromatase (enzyme responsible for the peripheral conversion of androgens to estrogens). Only used in postmenopausal women (estrogens produced peripherally).

-  Agent of choice for postmenopausal women with hormone receptor + breast cancer -  Drug names: Anastrazole, Letrozole, Exemestane

ERDs (Estrogen Receptor Downregulators) -  Inhibit the growth of breast cancer cells by competitive antagonism of the estrogen receptor (ER). Work to degrade the estrogen receptor.

-  Used in postmenopausal women for metastatic, advanced stage breast cancer when other hormonal therapies fail

-  Drug name: Fulvestrant Mouridsen HT, Rose C, Brodie AH, Smith IE. Challenges in the endocrine management of breast cancer. Breast. 2003;12 Suppl 2:S2-19.

Breast Cancer Hormonal Therapies Mechanisms

http://www.medscape.org/viewarticle/837672_2

Hormonal Therapy Associated Bone Loss ●  Estrogen = suppressive effect on

osteoclasts during bone remodeling favoring bone formation

●  Estrogen suppressed by AI’s/SERM’s = osteoclasts activity increases, increasing bone resorption

Ultimately Net Bone Loss

Pathophysiology of Prostate Cancer

Androgen Deprivation Therapies & Mechanisms

Type Explanation

Bilateral orchiectomy - surgical removal of both testicles - considered ADT because it removes the main source of testosterone production

LHRH agonists - luteinizing hormone releasing hormone -blocks the signal to the testicles to make testosterone thus reducing the level in the blood - when first given, testosterone levels briefly increase before falling to low levels -injected or placed as small implant under skin -given once a month or once a year depending on drug given

LHRH antagonist or gonadotropin-releasing hormone (GnRH) antagonist

- stops the testicles from producing testosterone - reduces levels in blood more quickly - monthly injection - can cause allergic reaction

Anti-androgens - block testosterone from binding to androgen receptors - taken as pills - used as a combination treatment

Dueregger A, Heidegger I, Ofer P, et al. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Nutrients. 2014;6(10):4491-4519.

Side Effects of ADT

Dueregger A, Heidegger I, Ofer P, et al. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Nutrients. 2014;6(10):4491-4519.

Cancer Treatments and BMD Loss: Men vs Women

AI: aromatase inhibitors CIOF: Chemotherapy Induced Ovarian Failure

ADT: Androgen Deprivation Therapy GnRH agonist: Gonadotropin-releasing hormone agonist therapy,

Lustberg MB, Reinbolt RE, Shapiro CL. Bone health in adult cancer survivorship. J Clin Oncol. 2012;30(30):3665-3674.

Review of Literature

Prevalence of Bone Loss in BC Patients

Healthy postmenopausal women

Lose approximately ~1% BMD per year

Postmenopausal women with breast cancer

Lose approximately 2-3 fold more per year

Chen Z, Maricic M, Bassford TL, et al. Fracture risk among breast cancer survivors: Results from the women's health initiative observational study. Arch Intern Med. 2005;165(5):552-558. Brown SA, Guise TA. Cancer-associated bone disease. Curr Osteoporos Rep. 2007;5(3):120-127.

Methods Results Notes

-Meta-analysis - 16 trials Calcium and Vitamin D supplement & bone health in females with BC -Trials found via Pubmed 1990-2012, excluded no comparison /placebo group - Anti resorptive drugs in addition to Calcium and Vitamin D

-Results from 16 trials = 500-1500 mg Ca and 200-1000 IU of Vitamin D/day not enough to prevent loss of BMD % - Some trials did not include an unsupplemented placebo comparison group - Conclusions regarding supplementation vs no supplementation cannot be made

-Limitations: - No specification of amount of elemental Ca (biologically active) provided/consumed - No dietary recall - Studies varied in length -Other drugs not addressed

Datta M, Schwartz GG. Calcium and vitamin D supplementation and loss of bone mineral density in women undergoing breast cancer therapy. Crit Rev Oncol Hematol. 2013;88(3):613-624.

Calcium and Vitamin D Supplementation and Loss of Bone Mineral Density in Women Undergoing Breast Cancer Therapy (Datta et al., 2013)

Figure 1a. Percent Change in Bone Mineral Density in Supplemented Premenopausal Women

Authors of Various Trials Looking at Ca/Vitamin D Supplementation and BMD in Premenopausal Women

Datta et al., 2013 500 -1000 Ca / 400 - 1000 IU Vitamin D

Figure 1b. Percent Change in Bone Mineral Density in Postmenopausal Women

Authors of Various Trials Looking at Ca/Vitamin D

Supplementation and BMD in Postmenopausal

Women

Of Note: Rastelli: 2 different groups in trial: ●  * = Ca/Vit D ●  *1 = additional Vit D

group (50,000 IU D2)/ week

Markopoulos: groups based off T-score: ●  + = anastrozole ●  +1 = anastrozole +

risendronate Van Poznak: groups based off anastrozole and/or placebo: ●  # = anastrozole ●  #1 = anastrozole +

placebo or risedronate

Datta et al., 2013

Methods Results Notes

- Observational - Subjects self reported BC diagnosis -Subjects > 50 years of age, with osteoporosis or osteopenia -Control = 800-1000 IU Vitamin D, 1500 mg Calcium (from diet and supplements combined) - Intervention = Alendronate, Etidronate + 800-1000 IU Vitamin D, 1500 mg Ca

- 70 final subjects - One year from baseline, lumbar BMD: - Control: decreased 1.4% - Intervention:

-  increased 2.3% in Etidronate -  Increased 4.3% in Alendronate patients

Overall, Alendronate tx was associated with greater improvements in lumbar spine BMD as compared to Etidronate, Calcium and Vitamin D

- Limitations: -No food frequency questionnaires or diet history included - Subjects were advised to consume Ca and vit D in diet, yet unclear how this was measured - Small sample size - Accuracy of BC diagnosis unknown due to self reporting - Other treatment therapies were not obtained

Sawka AM, Ioannidis G, Papaioannou A, et al. Are oral bisphosphonates effective in improving lumbar bone mineral density in breast cancer survivors with osteopenia or osteoporosis? J Obstet Gynaecol Can. 2005;27(8):759-764.

Are Oral Bisphosphonates Effective in Improving Lumbar Bone Mineral Density in Breast Cancer Survivors with Osteopenia or Osteoporosis?

(Sawka et. al, 2005)

* Analysis adjusted for current Tamoxifen use, # of previous vertebral fractures, time since cancer diagnosis, age, and L2-L4 BMD

Sawka et al. 2005

Prevalence of Bone Loss in PC Patients Men with Prostate Cancer prior to initiating ADT

Osteopenia - 37%

Osteoporosis - 42%

Men with Prostate Cancer after initiating ADT

Osteoporosis - 53%

A decrease in bone mineral density can occur as early as 6 months after initiating ADT

Majority of loss occurs in the first year, with slow decreases in sequential years

Not all individuals develop osteoporosis

Type of ADT treatment, lifestyle factors and genetic predispositions

Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: A critical review. Oncologist. 2012;17(9):1171-1179.

Calcium and Vitamin D Intake Among Men -- Recommendations

Calcium and Vitamin D Intake Among Men -- Reality

Calcium (mg) Vitamin D (IU)

Age Group RDA UL RDA UL

51-70 years 1000 2000

600 4000

>70 years 1200 800

Institute of Medicine 2010

NHANES Survey 2003-2006 Age Group Calcium (mg) Supplement Use (Ca) Vitamin D (IU) Supplement Use (Vit D)

51-70 years 951mg +/- 19 mg per day MVMM: 40% Ca: 51% 204 IU +/- 12 IU per day 40%

>70 years 871 +/- 25 mg per day MVMM: 43% Ca: 56% 224 IU +/- 16 IU per day 49%

Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: A critical review. Oncologist. 2012;17(9):1171-1179.

Methods -Meta-analysis -12 clinical trials -Extracted from PubMed searches (2003-2010) -Excluded trials that did not include Ca/Vit D or did not measure BMD -# of subjects varied between 40-222 with one of 1,468 -most followed for 12 months of treatment -most subjects with non-metastatic PC

Calcium and Vitamin D Supplementation During ADT for Prostate Cancer: A Critical Review (Datta et al , 2012)

Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: A critical review. Oncologist. 2012;17(9):1171-1179.

Datta et al, 2012 Clinical Trials

Amount of Ca/Vit D doses prescribed in various clinical trials

Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: A critical review. Oncologist. 2012;17(9):1171-1179.

Percent change in lumbar spine BMD within the comparison groups reported in various clinical trials

Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: A critical review. Oncologist. 2012;17(9):1171-1179.

A1

B1

<1 year

>1 year

Datta et al, 2012 Conclusions Limitations

-Supplementation of 500-1000 mg Ca and 200-500 IU of Vitamin D is inadequate to prevent BMD loss in PC patients undergoing ADT -Supplementation may be beneficial with prolonged intake/treatment -No conclusive statement can be made regarding supplementation effectiveness in ADT-related bone loss

-Many of the trials did not provide how much elemental calcium was provided or consumed

-Amount of calcium taken in from dietary sources was not stated

-Assessment of adherence was not provided

Bone Mineral Density Changes in Patients with Prostate cancer during the first 2 years of ADT (Morote et al, 2006)

Methods

-Prospective study -62 patients with nonmets PC -31 patients on ADT (study group) -31 patients s/p prostatectomy (control) -measured BMD with DXA at baseline and 1 year for control and every year for ADT group -looked at BMD loss in 5 locations

BMD changes after 1 year of ADT (Morote et al, 2006)

Contradictory Studies

How much is too much for women?

Calcium/Vitamin D Supplementation and Coronary Artery Calcification in the Women's Health Initiative

-  Manson et al., 2010

-  Subjects randomized to 1000 mg Ca and 400 IU Vitamin D or placebo group

-  No differences found between intervention and placebo groups in terms of coronary artery measurements

-  Overall, no risk between supplementation and coronary artery calcification found

-  Limitation: Women in placebo group continued to take personal Ca/Vitamin D supplements

Manson JE, Allison MA, Carr JJ, et al. Calcium/vitamin D supplementation and coronary artery calcification in the women's health initiative. Menopause. 2010;17(4):683-691.

Associations of Dietary Calcium Intake and Calcium Supplementation with Myocardial Infarction and Stroke Risk and Overall Cardiovascular Mortality in the Heidelberg Cohort of the European Prospective Investigation into Cancer

and Nutrition Study (EPIC-Heidelberg) EPIC Heidelberg Study

-  11 year German observational cohort -  Subjects asked at baseline if they took Ca

supplements. *No data on dosage -  Women completed FFQ to determine dietary Ca

intake -  Results: women who consumed Ca supplements had

a significantly higher incidence of MI as compared to those who did not (HR = 2.39; 95% CI: 1.07-1.45).

-  Not conducted specifically on BC patients

*Of note: Incidence of kidney stones has been found with high Ca intakes > UL, encouraging the U.S. Preventive Services Task Force (USPSTF) to recommend that healthy, postmenopausal women avoid Ca supplementation of greater than 1000 mg/day and/or 400 IU vitamin D/day

Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the heidelberg cohort of the european prospective investigation into cancer and nutrition study (EPIC-heidelberg). Heart. 2012;98(12):920-925.

How much is too much for men?

Milk and Dairy Consumption among Men with Prostate Cancer and Risk of Metastases and PC death

Pettersson et al (2012)

Pettersson A, Kasperzyk JL, Kenfield SA, et al. Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. Cancer Epidemiol Biomarkers Prev. 2012;21(3):428-436.

Study Type Methods Results

Prospective Cohort Study developed from the Health Professionals Follow-Up Study

- 3918 men diagnosed with localized PC - Milk and dairy intake assessed through multiple questionnaires - PC outcomes: metastases and death - Cox proportional hazard models - Intake was assessed in servings/day and categorized into quintiles -Dairy was categorized into low fat/full fat -median follow up time = 7.6 years

- 229 cancer deaths - 69 distant metastases -Total Milk and Total dairy was not associated with progression of PC - Highest intake of low fat dairy had a decreased risk of progression vs lowest intake of low fat dairy -Higher intake of whole milk had an increased risk of progression of PC compared to lowest intake of whole milk

Dairy Intake and Progression of Prostate Cancer

Pettersson A, Kasperzyk JL, Kenfield SA, et al. Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. Cancer Epidemiol Biomarkers Prev. 2012;21(3):428-436.

Reflecting on the literature….

Strengths and Weaknesses of the Literature WEAKNESSES

Minimal RCTs on effect of supplementations (without medications)

Multiple studies include subjects currently receiving treatment- hard to target survivors specifically

Low n’s = inadequate power

Short time frames

Barely assess Ca/Vit D diet intake

If assessed, FFQs are used

Type of Ca consumed not specified (i.e elemental vs non elemental)

Without 25OH Vitamin D can’t judge the contribution of sunlight derived vitamin D

STRENGTHS

Specifically targeted breast and prostate cancer patients

Utilized DXA for BMD measurements (gold standard)

Professional Organization Population Calcium (mg/day) Vitamin D (IU/day)

American Society of Clinical Oncology (ASCO) PC survivors post treatment </= 1200 (from dietary sources)

>/= 600

ASCO’s patient information website (Cancer.net) PC patients undergoing ADT 1000-1500 (elemental source)

400-800

National Guideline Clearinghouse PC patients undergoing ADT 1500 2000

European Association of Urology (EAU) PC patients undergoing ADT 1200 1000

National Osteoporosis Foundation (NOF)//National Comprehensive Cancer Network (NCCN)

Healthy men < 70 years

1000 400-800

Healthy Men > 70 years and

1200 800-1000

Prostate Cancer Research Institute PC patients Diet + 1200-1500 mg from Ca Citrate

2000

The Bone and Cancer Foundation PC patients 1000-1500 800-1200

Prostate Cancer Foundation Limit daily calcium intake to <1500 mg for preventing PC Gives no recommendations for bone health during ADT

Mayo Clinic Maintaining Calcium intake to below the tolerable upper limit of 2000

Harvard School of Public Health Advises men not to exceed the RDA for Calcium and to limit the intake of Ca supplements to 500mg if adequate dietary calcium intake cannot be maintained

What should we recommend to our patients? Prostate Cancer

On ADT

Calcium: Total 1200-1500 mg/day From diet (Low fat dairy/milk) + supplement*

Vitamin D: Total 600 IU/day From diet + sunlight + supplement* *Supplements warranted only if patient can’t meet recommendations through diet

Professional Organization Population Calcium (mg/day) Vitamin D (IU/day)

American Society of Clinical Oncology (ASCO) Women with BC 1200 400-600

The Belgian Bone Club Women with BC on treatment 1200-1500 400-800

National Guideline Clearinghouse Women with BC 1500 2000

National Comprehensive Cancer Network (NCCN)

Young women at risk for developing treatment induced bone loss and women > 50 years

1200 800-1000

The European Society for Clinical and Economical Aspects of Osteoporosis and Osteoarthritis (ESCEO)

BC patients 1000 > 800 IU/day or 10,000 IU/week

Breastcancer.org BC patients 1200 for women > 50 years - 400 for women 50-70 years - 600 for women > 70 years

Living Beyond Breast Cancer BC Patients 1000-1500 400-1000

Current Clinical Practice Guidelines

What Should we Recommend to our Patients? Breast Cancer

Premenopausal Postmenopausal

Calcium: Total 1500 mg/day* From food sources and supplement

Vitamin D: Total 400 IU/day From diet + sunlight + supplement

Calcium: Total 1500 mg/day* From food sources and supplement

Vitamin D: Total 800 IU/day* From diet + sunlight + supplement

* If kidney stones are found, recommend 1000 mg/day Ca, and 400 IU Vitamin D per USPSTF guidelines

Overall Recommendations -  Routine bone density screening

-  May aid in reducing unnecessary drug therapies (i.e bisphosphonates)

-  Bisphosphonates proven effective

-  Nonpharmacologic recommendations for bone health:

-  Weight bearing exercise

-  Regular physical activity

-  Tobacco product cessation

-  Limit alcohol consumption

-  Regular patient to physician dialogue throughout survivorship

-  Adequate Ca and Vitamin D from dietary sources

Calcium Food

Sources

Food Serving Calcium (mg)

Tofu prepared with calcium sulfate (raw) ½ cup 434

Yogurt, plain, low-fat 8 ounces 415

Sardines, canned 8 ounces 325

Cheddar cheese 1.5 ounces 303

Milk 8 ounces 300

Fortified orange juice 8 ounces 300

Almond milk, rice milk, soy milk (fortified) 8 ounces 300

Mozzarella, part skim 1 ounce 210

White beans (cooked) ½ cup 81

Bok Choy (cooked) ½ cup 79

Orange 1 medium 60

Kale (cooked) ½ cup 47

Broccoli (cooked) ½ cup 31

Red beans (cooked) ½ cup 25

Vitamin D Food

Sources

Food Serving Vitamin D (IU)

Cod liver oil 1 TBSP 1360

Salmon, cooked 3-½ oz 360

Mackerel, cooked 3-½ oz 345

Tuna fish, canned in oil 3 oz 200

Sardines, canned in oil 1-¾ oz 250

Orange juice, fortified 8 oz 100

Milk, fortified 1 cup 98

Cereal, fortified 1 cup 40

Egg 1 egg 20

Liver, beef, cooked 3-½ oz 15

Cheese, Swiss 1 oz 12

Non-food source: Sunlight

Future Research Needed on this Topic: We need your help!

Based on what we have presented on the past literature… If you were to propose a research study on this topic, what would you investigate?

What would be your treatment group (s)?

What would be your outcome variables?

Our Studies would be: Breast Cancer

RCT, 2 years

n = 300

Study population: BC Survivors (not on treatment)

Intervention group 1: 1. Postmenopausal: 1500 mg Ca, 800 IU vitamin D per day 2. Premenopausal: 1500 mg Ca, 400 IU per day

Intervention group 2: Postmenopausal & Premenopausal: RD counseling on how to increase dietary calcium and vitamin D intake, no supplementation. Intakes measured via FFQ

Control group: No supplementation. Normal diet

Outcome variables: Changes in BMD (lumbar spine, femoral neck), # of fractures/ broken bones, # of CVD events

*Assess baseline deficiencies via FFQ screeners of vitamin D and calcium intake or previous BMD tests

Prostate Cancer

RCT, followed through entire treatment phase or at least 2 years

n = 300

Study population: PC patients starting ADT

Intervention group 1: 1200 mg Ca from supplement + 600 IU from Vitamin D supplement

Intervention group 2: RD counseling on how to increase dietary calcium and vitamin D intake, no supplementation

Control group: No supplementation. Normal diet.

Outcome variables: Changes in BMD (lumbar spine, femoral neck), # of fractures/ broken bones, progression of PC

*Assess baseline deficiencies via FFQ screeners of vitamin D and calcium intake or previous BMD tests

QUESTIONS???

Actual Practice Alibhai et al, 2006 Retrospective

Survey Study -Survey sent to Canadian urologists and radiation oncologists -questions regarding current practice of BMD testing, treatment practices, risk of osteoporosis in 60 year of men starting ADT

-58% response rate (170 of 294 respondents) - few said they order a baseline BMD - 40% would order a repeat BMD test after starting ADT if baseline showed normal BMD or if BMD was unknown - 66% would order a repeat BMD test if baseline showed osteoporosis In patients with normal BMD respondents: -58% would recommend weight bearing exercises -50% would recommend Ca supp -47% would recommend Vit D supp - 6% would recommend bisphosphonate supp -Those with osteoporosis at baseline, 44% respondents recommend bisphosphonates

-physicians are not ordered BMD tests at baseline regularly - 44% are using bisphosphonates to treat established osteoporosis and hardly using it for prevention

Prevalence of Compromised Bone Health Among Overweight and Obese African-American Breast Cancer Survivors(AA BC): A case-control study

Author/Year Methods Results Notes

Sheean et al., 2015 -Subjects a sub sample of a RCT targeting AA BC survivors for weight loss -Recruited through UIC -Completed tx at least 6 months prior to trial -All subjects were overweight/obese (BMI 25-30 kg/m2) -BC subjects completed Block 2005 FFQ - Non-Cancer comparison group obtained from NHANES 2007-2010 -n = 111

-  BMD: BC survivors had significantly lower femoral neck BMD (p = 0.007)

-  No differences found in osteoporosis prevalence (p = 0.263)

-  Total Energy intake and Ca intake highest in BC survivors

-  Results challenge assumptions that BC survivors are at risk for bone disease

-  Results suggest survivor bone implications differ by race and body weight

-  Limitations: -  1. Overweight/obese women included -  2. Treatment, diagnosis information self reported -  3. Time of study (2011-2013) recruitment did not

match time of NHANES case control comparison (2007-2010)

-  Different dietary assessments used between groups

Sheean P, Liang H, Schiffer L, Arroyo C, Troy K, Stolley M. Assessing the prevalence of compromised bone health among overweight and obese african-american breast cancer survivors: A case-control study. J Cancer Surviv. 2016;10(1):21-30.

Table 3. Bone Health Characteristics and dietary intake factors of African-American breast cancer survivors and their age, race, and BMI matched non-cancer population controls from NHANES 2007-2010

Sheean et al., 2016

Calcium Intake and Prostate Cancer Among African Americans: Effect Modification by Vitamin D Receptor Calcium Absorption Genotype (Rowland et al, 2012)

Study Type Methods Conclusions

Case-Control -533 AA prostate cancer cases --256 with advanced stage, 277 localized stage -250 AA matched controls -FFQ to assess calcium intake -Calcium was categorized into quartiles -AA genotype = high intestinal calcium absorption -GG phenotype = poor intestinal calcium absorption

-greater risk of PC was found in men with higher dietary calcium intake and a high intestinal calcium absorbing (AA) genotype -men in the highest calcium intake quartile (>1059mg/d) had a >2 fold increased risk of prostate cancer (local or advanced) compared to men in the lowest intake group (<488 mg/d) -Supplement consumers of >400mg/d had increased risk for advanced prostate cancer -those with GG phenotype has a significantly lower risk of advanced PC

Total, Dietary, and Supplemental Calcium

Intake and

Prostate Cancer Among African

Americans (Rowland et al, 2012)

Rowland GW, Schwartz GG, John EM, Ingles SA. Calcium intake and prostate cancer among african americans: Effect modification by vitamin D receptor calcium absorption genotype. J Bone Miner Res. 2012;27(1):187-194.